Renal toxicity and biokinetics models after repeated uranium instillation.

Area of Science:

• Toxicology
• Environmental Health
• Nuclear Science

Background:

• Occupational exposure to uranium compounds during nuclear fuel processing is a concern.
• Uranium nephrotoxicity is established after acute exposure but debated after chronic exposure.

Purpose of the Study:

• To establish the nephrotoxicity threshold of uranium following repeated upper airway exposure.
• To compare uranium biokinetics with existing models after protracted exposure.

Main Methods:

• Mice were intranasally instilled with uranyl nitrate (0.03-3 mg/kg/day) four times weekly for two weeks.
• Uranium levels in urine and tissues were monitored from day 1 to 91 post-exposure.
• Nephrotoxicity was assessed via biomarkers (KIM-1, clusterin, osteopontin), renal function imaging (Doppler-ultrasonography), and histopathology.

Main Results:

• Uranium retention in organs and excreta generally reflected exposure levels, except for renal retention at the highest dose.
• Nephrotoxicity biomarkers and altered renal function were observed between days 4 and 21.
• The nephrotoxicity threshold was identified between 0.25 and 1 mg/kg/day.

Conclusions:

• Repeated uranium inhalation exposure can induce nephrotoxicity and alter uranium biokinetics.
• Existing biokinetic models may require modification to account for uranium-induced kidney damage.
• A specific threshold for repeated uranium exposure via the upper airways was determined.